Overview

Background

Merck is developing MK-7622 as an add-on therapy to the cholinesterase inhibitor donepezil for the treatment of Alzheimer's disease. No studies have been published on this compound in the peer-reviewed literature or other publicly available documents. Merck has published on its preclinical research in mice and rhesus monkeys of allosteric M1 muscarinic agonists, which would enhance the effect of acetylcholine neurotransmission and could be suitable as adjunct therapy to cholinesterase inhibitors (see Aug 2009 news; Uslaner et al., 2012; Lange et al 2015). MK-7622 appears to have grown out of this program.

Findings

No information about Phase 1 clinical studies of MK-7622 is available in the public domain. In October 2013, Merck began a Phase 2 trial in the United States to evaluate the compound's tolerability and efficacy as a symptomatic adjunct to donepezil therapy in patients with probable AD as diagnosed by two conventional diagnostic criteria, the NINCDS-ADRDA and DSM-IV.

This multicenter trial was to use two stages to compare three doses of MK-7622, given once daily as capsules. Stage 1 randomized participants to receive either placebo or 45 mg of MK-7622 for six months, and interim analysis was to determine if the trial proceeds to Stage 2. Stage 2 was to randomize a separate group of participants to receive either placebo or 5, 15, or 45 mg of MK-7622 for six months. The primary outcome measures were change from baseline in the ADAS-Cog11 at three months, the number of patients who have an adverse event, and the number of patients who drop out of the trial. This trial does not employ biomarkers.

This trial was set to enroll 830 patients and run until 2020; however, in March 2016, it stopped recruiting and in April it was terminated at 240 participants. Accessed November 2016, Merck's Phase 2 and 3 development pipeline no longer listed MK-7622. No study results were published, or posted on Merck's website.